Membrane Transport Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Annu Rev Physiol. 2012;74:69-86. doi: 10.1146/annurev-physiol-012110-142317.
Lysosomes, the terminal organelles on the endocytic pathway, digest macromolecules and make their components available to the cell as nutrients. Hydrolytic enzymes specific to a wide range of targets reside within the lysosome; these enzymes are activated by the highly acidic pH (between 4.5 and 5.0) in the organelles' interior. Lysosomes generate and maintain their pH gradients by using the activity of a proton-pumping V-type ATPase, which uses metabolic energy in the form of ATP to pump protons into the lysosome lumen. Because this activity separates electric charge and generates a transmembrane voltage, another ion must move to dissipate this voltage for net pumping to occur. This so-called counterion may be either a cation (moving out of the lysosome) or an anion (moving into the lysosome). Recent data support the involvement of ClC-7, a Cl(-)/H(+) antiporter, in this process, although many open questions remain as to this transporter's involvement. Although functional results also point to a cation transporter, its molecular identity remains uncertain. Both the V-ATPase and the counterion transporter are likely to be important players in the mechanisms determining the steady-state pH of the lysosome interior. Exciting new results suggest that lysosomal pH may be dynamically regulated in some cell types.
溶酶体是内吞途径的终末细胞器，可消化大分子物质，并将其成分作为营养物质提供给细胞。溶酶体内部存在着针对广泛靶标的水解酶；这些酶通过细胞器内部的高度酸性 pH（4.5 到 5.0 之间）而被激活。溶酶体通过质子泵 V 型 ATP 酶的活性来产生并维持其 pH 梯度，该酶利用 ATP 的代谢能量将质子泵入溶酶体腔中。由于这种活性分离了电荷并产生了跨膜电压，因此必须有另一种离子移动以耗散该电压才能实现净泵送。这种所谓的反离子可以是阳离子（从溶酶体中移出），也可以是阴离子（进入溶酶体）。尽管对于这种转运蛋白的参与仍有许多悬而未决的问题，但最近的数据支持 ClC-7（一种 Cl(-)/H(+)反向转运蛋白）参与了这一过程。尽管功能结果也指向阳离子转运体，但它的分子身份仍然不确定。V-ATP 酶和反离子转运体可能都是决定溶酶体内部稳态 pH 的机制中的重要参与者。令人兴奋的新结果表明，在某些细胞类型中，溶酶体 pH 可能是动态调节的。
